Concussions affect hundreds of thousands of athletes each year. To learn more about this "invisible injury," Princeton researchers Annegret Dettwiler-Danspeckgruber (right), an associate research scholar at the Princeton Neuroscience Institute, and Margot Putukian (left), the director of athletic medicine and head team physician for University Health Services, are engaged in ongoing work to study sports-related concussions. Here, they review brain scans from the magnetic resonance imaging machine at the Princeton Neuroscience Institute.

Photo by Brian Wilson

Featured Story

Concussion research aims to help athletes, study of the brain

Posted October 17, 2011; 12:00 p.m.

by Emily Aronson

It's called an invisible injury, yet it affects hundreds of thousands of athletes each year. From professional boxers and college football stars, to high school soccer players and kids competing in schoolyard baseball games, concussions can be a significant injury for anyone playing sports.

To address the problem, Princeton researchers Annegret Dettwiler-Danspeckgruber and Margot Putukian have spent the past four years studying sports-related concussions, aiming to improve diagnostic tools and help better determine when it's safe for athletes to return to play. Their work is ongoing, but by bridging neuroscience and sports medicine, they are seeking not only to support athletes, but also to illuminate the study of both brain structure and function following concussion.

The two are in the midst of a study following concussed student-athletes for two months after injury. The work centers on the use of new techniques to study brain injury -- functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) scans. The study investigates how the findings from these techniques compare and possibly correlate to findings on clinical measures of symptoms, the results of a neurologic exam that include cognitive evaluation and balance, and the outcomes of formal neuropsychological testing.

"We hope to further understand how the brain recovers from what is a common, though often underreported, injury in athletics," said Dettwiler. The Centers for Disease Control (CDC) and Prevention estimates that 1.6 million to 3.8 million sports concussions may occur annually.

Dettwiler and Putukian are bridging neuroscience and sports medicine in their research on concussion. They are seeking not only to support athletes, but also to illuminate the study of both brain structure and functions following concussion. Here, Dettwiler (right) and Murali Murugavel (left), a postdoctoral researcher at Princeton's neuroscience institute (PNI), prepare a participant for diffusion tensor imaging and fMRI scans. (Photo by Brian Wilson)

The Princeton team's research could aid the development of more sophisticated ways to evaluate and manage concussions.

"The implications of Margot and Annegret's collaboration could be significant. Sports-related concussions have been considered a transient problem in neurological function brought on by a trauma -- that is, it's been thought to be a problem of brain function, not necessarily brain structure," University Health Services Director John Kolligian said. "Using brain-imaging techniques, their initial research suggests that concussive injuries also involve structural changes in the brain."

Their work comes at a time when the national media have cast a spotlight on the short- and long-term ramifications of concussions, as well as the Ivy League's recent adoption of stringent measures for football. According to Putukian, these include limiting the number of days of full-contact practices, enforcing rules related to illegal hits, and increasing the education of athletes and coaches about the condition.

"The imaging study that Margot Putukian and Annegret Dettwiler are doing is fundamentally important because it may be a way to objectively diagnose a concussion," said Stanley Herring, a clinical professor at University of Washington Medicine, who also is team physician for the Seattle Seahawks football team and member of the NFL Head, Neck and Spine Committee. "Right now we think we know what a concussion is, but their work could tremendously advance our ability to study and understand this injury."

This diffusion tensor imaging scan of the human brain represents a combined image of the fiber tracts (nerve fibers that connect one area of the brain with another) located in the white matter of the brain of a group of 10 athletes who sustained a concussion and a control group of 10 athletes with no history of concussion. The three-dimensional scan shows the average image of all the white matter fiber tracts of the 20 subjects, with the center of the fiber tracts marked in green lines. The areas of the brain colored in red to yellow represent locations in which the concussed athletes show alterations in their white matter fiber tracts. The bottom images zoom in on the two main areas where the differences were found. (Image courtesy copyright Cubon et al. J Neuroscience 28:1-13, 2011)

Bridging academic research and sports medicine expertise

While there has been growing public attention on how concussions affect physical and mental health following recent studies, such as early-phase research on Alzheimer's disease and other conditions in professional football players with repeated head injuries, Dettwiler and Putukian separately studied brain trauma for many years before each arrived at Princeton in 2004.

Putukian, who received her medical degree from the Boston University School of Medicine, has been involved in national and international concussion management efforts, including serving as a consultant for the NCAA and the Centers for Disease Control. She also is currently on the NFL Head, Neck and Spine Committee. Dettwiler, who received her Ph.D. from Columbia University, worked with traumatic brain injury patients at the nonprofit organization Bancroft NeuroHealth.

Murugavel, seated in the scanner console room at PNI, prepares to collect data from a brain scan. (Photo by Brian Wilson)

The pair began collaborating in 2008, and their current work using fMRI and DTI scans surpasses the abilities of traditional medical imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI) scans, which can show more serious brain injury such as skull fracture or intracranial bleeding, but are not sensitive enough to detect subtle changes in the brain due to concussion, Dettwiler explained.

"Concussions can be challenging because unlike other injuries, there is no one, definitive test or marker that easily sorts out whether or not someone has an injury, or how severe it is," Putukian said. "You can't 'see' them the way you would a broken bone -- rather you combine several components such as symptoms and clinical and cognitive evaluations to make a diagnosis."

"One of our research questions is do we pick up something from these imaging techniques that we're not able to observe through the usual clinical evaluations used today?" she continued.

For the study, Dettwiler's team performs the neuroimaging component, including the acquisition image analysis and interpretation of DTI scans of concussed subjects to track changes in brain structure, as well as fMRI scans to examine whether their brains function differently while performing simple and complex tasks.

This research, in which Princeton's student-athletes participate voluntarily, is done in conjunction with a comprehensive concussion program in which varsity athletes already are involved, which includes preseason as well as post-injury assessments.

The preseason exam includes a standardized neurological screening known as a sideline concussion assessment. The screening incorporates evaluating symptoms and giving cognitive and balance tests, along with computerized and sometimes paper-and-pencil neuropsychological testing. Administered by the athletic training and medical staff, neuropsychological tests measure brain behavior relationships and include tests evaluating verbal and visuospatial memory, immediate and delayed memory function, attention span, reaction time, tracking abilities, and processing speed.

The staff also obtains information regarding modifying factors that may prolong recovery -- such as prior concussion, headache disorders, attention deficit hyperactivity disorder (ADHD) and learning disabilities, depression and anxiety -- as part of the confidential preseason exam. In addition, athletes learn about the importance of reporting injuries, including those that may be indicative of concussion.

When an athlete participating in the research sustains a concussion, they are evaluated by the athletic medicine staff using the sideline assessment tool. Subsequently, athletes perform the more comprehensive battery of neuropsychological testing, with both computer and paper-and-pencil testing. Administered by the athletic training staff, the findings are then interpreted by an outside consulting neuropsychologist, who compares them to the athlete's baseline information. This interpretation, along with the athlete's clinical information and modifying factors, are used by the team physician to make individualized management and return-to-play decisions.

Techniques may detect structural differences in the brain

While their work is ongoing, Dettwiler and Putukian hypothesize the DTI, fMRI and other evolving MRI techniques may demonstrate structural differences in injured athletes' brains, which may correlate with deficits in cognitive function found via the subjective, clinical and neuropsychological tests currently used to diagnose concussions. They also are tracking brief measures of depression and anxiety before and after concussion.

Their current research builds on their pilot study published in the Journal of Neurotrauma in February 2011 with former Princeton neuroscience postdoctoral fellow Valerie Cubon and Cynthia Boyer of Bancroft NeuroHealth. In that study, DTI scans were performed on 10 concussed student-athletes with prolonged symptoms such as headaches, dizziness and trouble concentrating, which they experienced for at least six weeks to more than a year. The scans provided evidence of structural differences in the brain, suggesting that DTI may be a useful tool to evaluate concussive injury.

While other studies have used DTI scans to capture structural changes following more severe trauma, Dettwiler said their current work aims to push the technology further, exploring if scans are sensitive enough for patients with mild concussions.

"It's currently not feasible to widely use DTI and fMRI scans outside of a research setting," Dettwiler said, noting that the imaging "can only be used in a group comparison and is not yet developed to assess structural changes in individual brains."

Putukian added, "We do not know what the differences mean clinically, or how they correlate to clinical findings, if at all." She said that while the DTI and fMRI scans are not yet ready for clinical use, she and Dettwiler are "hoping our work can help spur the development of technological tools that one day can be used in the clinical environment."

While acknowledging their research "is just one piece of the puzzle," the two are hopeful they can elucidate some important questions.

"We're very interested to see if there tends to be a correlation between the severity of injury and what we observe through these advanced brain-imaging techniques," Putukian said. "Are the scans of an athlete who takes months to recover different from the athlete who appears to be better in five days?"

Even if they do not discover such a correlation, Dettwiler said, they may find that DTI and fMRI scans observe that changes persist in the brain even when an athlete appears to be symptom-free following traditional medical tests and/or neuropsychological tests. This could influence the decision to learn when it's truly safe for players to get back in the game -- a decision that is important in order to minimize risk for repeated injuries.

"If a DTI scan were to show that the brain is still injured a month after a concussion, that could lead to a major change in how concussions are treated," said Lester Mayers, director of sports medicine at Pace University, who has advocated for a longer time interval allowed for concussed athletes before return to play.

Putukian, shown with the Princeton football team at a practice, says that engaging students to participate in research helps reinforce growing awareness about the seriousness of concussions and the importance of early intervention. (Photo by Denise Applewhite)

Helping future student-athletes

According to Kolligian, in linking the University's neuroscience institute and University Health Services, Dettwiler and Putukian's partnership is a "bold example" of how research faculty and student-life professionals can leverage their distinctive perspectives to help students.

The clinical focus of their work is noteworthy given that Princeton does not have a medical school, Dettwiler and Putukian said, and Daniel Osherson, a professor of psychology affiliated with the institute, said their study "unites clinical and basic science perspectives."

"Concussion is a potentially serious medical condition; at the same time, it offers a window on fundamental aspects of brain structure and function," said Osherson, the Henry R. Luce Professor of Information Technology, Consciousness and Culture at Princeton.

Osherson is a research collaborator on Dettwiler and Putukian's current study, along with neuroscience postdoctoral fellow Murali Murugavel; assistant athletic trainer John Furtado; neuropsychologist Andrew Conway, a senior lecturer in Princeton's psychology department; neuropsychologist Ruben Echemendia; and Cubon, who is now an assistant professor of chemistry at Kent State University-Trumbull. Putukian added that Princeton's athletic trainers also are involved in the concussion program.

While their goals are long-term, the researchers said that simply engaging students to participate in research helps reinforce growing awareness about the seriousness of concussions and the importance of early intervention.

"It used to be 20 years ago a coach may have told an athlete with a minor head injury to 'shake it off.' That does not happen anymore," Putukian noted.

Senior Kelly Pierce, a member of the women's openweight crew team who served as a control subject for the study, said she would encourage her peers to report "even the smallest head trauma."

"Athletes should be more aware of concussions so they can receive proper treatment and stand a better chance of recovery, especially from more concussions that might occur in the future," Pierce said.

Men's lacrosse player Brian Reilly, who sustained a minor concussion during a practice last fall, said he was inspired to participate in the study because he has a brother involved in athletics who recovered from a series of concussions.

"Questions about concussions and their effects on athletes are all over the media today. The answers, however, are not," said Reilly, a sophomore. "Hopefully Dr. Putukian and Dr. Dettwiler's research will yield a more specific and practical treatment than what is currently available to concussed athletes, and will spare somebody some of the challenges that faced my brother."